This proposal requests funds to purchase a JEOL JEM-100SX transmission electron microscope to serve as a research instrument in support of 11 users with current NIH funding, two users with other government funding (NSF, NASA), and two others with other extramular funding (American Heart Association and Shriner's). Of those with NIH funding, two are NRSA postdoctoral fellows and one is a training grant for a predoctoral and postdoctoral student. All the users are from the Medical College of Wisconsin with the P.I. and all major users from the Department of Anatomy. The instrument requested is a state-of-the-art, "workhorse" instrument having few "down-time" problems. This instrument is being requested to replace an existing RCA-4A unit that is over 16 years old and has received heavy usage. The new unit would also have all the new advances made in resolution and imaging over that 16 year period. The instrument will be housed in the Department of Anatomy utilizing the space of the existing RCA. The Department of Anatomy also has 75% access to a three-year-old JEOL 100 CX instrument purchased by non-federal (private) funds. This excellent unit is used 25% by the biopsy program (Dr. Siegesmund) and is heavily committed to NASA research awards to Dr. Dan Riley, multiple Shriner's grants to Dr. Curtis and to collaborative interactions on an NIH proposal to Dr. Kalkhoff and Dr. Yorde (Co-P.I.). Much of the remaining time on this instrument is dedicated to a long running NIH award to Dr. Wong-Riley. All other requirements for TEM are dependent on the RCA unit. Use of this unit has reached a critical point largely as the result of the principal investigator relocating as departmental chairperson to the Medical College of Wisconsin. This change in grantee institution (for the P.I.'s grants) has resulted in the addition of several new, funded investigators to the department. Additionally, several new NIH grants have been awarded to the department, including two RO1's (Lough and Wong-Riley), a training award (Wong-Riley, co-investigator), and two new postdoctoral (NRSA) awards. The major users of the requested instrument who will form the Advisory Committee have many years of experience in electron microscopy and have published extensively using this research tool. There are also major contributors to BRSG programs. Mr. Ross Lepera, the individual assigned major maintenance responsibility, has had 13 years experience, including running a large centralized facility.